Role of bariatric surgery in reducing the risk of colorectal cancer: a meta-analysis.

BACKGROUND: Obesity increases the risk of multiple co-morbidities such as type 2 diabetes, cardiovascular disease and most cancers, including colorectal cancer. Currently, the literature presents conflicting results regarding the protective effects of bariatric surgery on the incidence of colorectal cancer. This meta-analysis was conducted to investigate the effect of bariatric surgery on the risk of developing colorectal cancer in obese individuals. METHODS: Ovid Embase, Ovid MEDLINE, Cochrane CENTRAL and Web of Science were searched for relevant articles. Articles published by the end of December 2018 were retrieved; data were extracted according to evidence-based PICO (population, intervention, control, outcome) model and analysed using a random-effects model to estimate the pooled relative risk (RR) and its 95 per cent confidence interval. The heterogeneity of studies was tested and quantified using Cochran's Q and I2 statistics. Meta-regression was used to investigate the association of year of study, region, mean length of follow-up and sample size with RR. RESULTS: Seven articles, involving a total of 1 213 727 patients, were included in the meta-analysis. The pooled estimate of the RR was 0·64 (95 per cent c.i. 0·42 to 0·98). The test of asymmetry found no significant publication bias. Meta-regression showed that sample size was a statistically significant factor (P = 0·037), but year of publication, region and mean duration of follow-up were not significant. CONCLUSION: Patients who underwent bariatric surgery had a greater than 35 per cent reduction in the risk of developing colorectal cancer compared with obese individuals who had no surgery.

ANTECEDENTES: La obesidad aumenta el riesgo de múltiples comorbilidades, como la diabetes tipo II, las enfermedades cardiovasculares y la mayoría de los cánceres, entre los que se incluye el cáncer colorrectal. En la actualidad, la literatura presenta resultados contradictorios sobre el efecto protector de la cirugía bariátrica en la incidencia del cáncer colorrectal. Este metaanálisis se llevó a cabo para investigar el efecto de la cirugía bariátrica sobre el riesgo de desarrollar un cáncer colorrectal en individuos obesos. MÉTODOS: Se realizó una búsqueda de artículos relevantes en Ovid Embase, Ovid Medline, Cochrane CENTRAL y Web of Science. Se recuperaron los artículos publicados hasta diciembre 2018 y los datos se extrajeron de acuerdo con el modelo PICO que se utiliza en la práctica de la medicina basada en la evidencia (población, intervención, control, resultado). Asimismo, los datos se analizaron mediante un modelo de efectos aleatorios para estimar el riesgo relativo combinado y su intervalo de confianza del 95%. La heterogeneidad de los estudios se comprobó y se cuantificó utilizando los estadísticos de Cochran Q y I2 . Se utilizó un análisis de metarregresión para investigar la asociación del año del estudio, región, tiempo de seguimiento medio (años), y tamaño de la muestra con el riesgo relativo. RESULTADOS: Para este estudio se incluyeron siete artículos en el metaanálisis final lo que representa un total de 108.070 pacientes. Los resultados mostraron que la estimación combinada del riesgo relativo fue de 0,64 con un intervalo de confianza 95% (i.c. 0,42- 0,98). De acuerdo con la prueba de asimetría, no hubo sesgo significativo de publicación. La metarregresión mostró que el año de publicación, región, y la media de seguimiento no fueron significativas, mientras que el tamaño de la muestra sí lo fue. CONCLUSIÓN: Los pacientes sometidos a cirugía bariátrica tuvieron más del 35% de reducción del riesgo de desarrollar cáncer colorrectal en comparación con individuos obesos no operados.

Selectivity of peptide ligands for the human incretin receptors expressed in HEK-293 cells.

The increase in insulin response to oral glucose compared with glucose given by intravenous injection is termed the incretin effect and is mediated by two peptide hormones secreted from the gut in response to nutrient intake: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 and GIP exert their insulinotropic effects through their respective receptors expressed on pancreatic ß-cells. Both the GLP-1 receptor and the GIP receptor are members of the secretin family of G protein-coupled receptors and couple positively with adenylate cyclase, resulting in an increase in intracellular cAMP. In the present study, we investigated the activity of six previously reported peptide ligands at both the GLP-1 and GIP receptors expressed on HEK-293 cells using a highly sensitive reporter gene assay. GLP-1 and GIP demonstrated almost 100,000-fold selectivity for their respective receptors. Exendin 4 (Ex-4), a long-acting GLP-1 receptor agonist, displayed considerable activity at the GIP receptor. Exendin 9-39 (Ex 9-39) was able to block activity at both the GLP-1 and GIP receptors, and Pro3GIP, a previously-reported GIP receptor antagonist, was shown to act as a partial agonist at the GIP receptor. These data highlight the need for more selective antagonists to study these therapeutically important receptors.

Conversional surgery: single-step conversion of laparoscopic adjustable gastric band to laparoscopic sleeve gastrectomy.

BACKGROUND: Although some patients attain good outcomes after adjustable gastric band (LAGB), a certain quantity have experienced complications and insufficient weight loss. The objective of this study is to assess the safety and outcome of laparoscopic sleeve gastrectomy (LSG) as a conversion surgery after a failed LAGB. METHODS: This is a retrospective analysis of 40 patients who received LSG as conversional surgery from 2009 to 2012 in Al Amiri Hospital, Kuwait. Data analyzed included percentage of excessive weight loss (EWL%), body mass index (BMI), and postoperative complications. Paired t test was utilized to evaluate total weight loss after both procedures. RESULTS: Among the 40 patients that underwent conversion surgery, the mean age was 36 years old, 34 (85 %) of which were females. Follow-up for LAGB was 1 to 11 years (median, 4.5 years) and 6 months to 3 years (median, 1 year) for LSG. Mean BMI before LAGB was 44 kg/m(2) (SD = 7.2) and mean weight was 117.2 kg (SD = 25.1). A percentage of 20 % achieved good outcomes and 7.5 % experienced complications and 60 % insufficient weight loss. Median EWL% achieved with LAGB was 11.5 %, and after LSG, a median EWL% of 56.9 % was recorded. After conversional surgery, a significant drop in BMI was noted with p value < 0.002. CONCLUSIONS: Laparoscopic conversion from LAGB to LSG may be considered as an alternative for patients with a failed LAGB procedure. However, a longer follow-up study is required to validate the results.

Severe recurrent achalasia cardia responding to treatment of severe autoimmune acquired haemophilia.

Acquired haemophilia A and severe acquired achalasia are both very rare conditions with unknown aetiology. Haemophilia A is a haemorrhagic disease induced by deficiency or malfunction of coagulation factor VIII. Congenital haemophilia is an inherited disease transmitted by the mother through X-linked inheritance and primarily affects males. However, acquired haemophilia A is a serious, sudden-onset, autoimmune disease that affects either sex. In addition, achalasia is a disease of the oesophagus caused by abnormal function of the nerves and muscles. It causes swallowing difficulties due to the inability of the lower oesophageal sphincter to relax during swallowing, leading to dysphagia, regurgitation and chest pain. In this report, we describe the case of a patient with severe, newly diagnosed, acquired haemophilia A with long-standing, recurrent achalasia; the achalasia had recurred 3 times despite complete and proper surgical fixation. Acquired haemophilia A is treated with immunosuppressive therapy. High-dose steroid therapy was administered for 7 months, during which the patient responded well; moreover, the achalasia did not recur for more than 2 years. The response of the achalasia to immunosuppressive therapy suggests that achalasia may be an autoimmune disorder and that there may be an association between both diseases. The findings of the present case suggest that achalasia may favourably respond to steroid therapy as a first-line treatment prior to surgery.

Pasteurella multocida septic shock following liver transplantation treated with drotrecogin alpha (activated).

Severe sepsis and progression to septic shock in solid organ transplant recipients is associated with a high mortality. We describe a fulminant case of septic shock in a liver transplant recipient caused by Pasteurella multocida, a gram-negative coccobacillus most commonly associated with domestic cats and dogs. P. multocida is a rare cause of bacteremia and has not been reported as a cause of septic shock following liver transplantation. In addition to standard therapy, the patient was managed with drotrecogin alpha (activated) recombinant activated protein C (APC), an evidence-based agent that has been shown to significantly improve outcome in severe sepsis in the non-transplant population. The known risk factors, clinical course, and outcomes of severe infection associated with P. multocida are also briefly reviewed. This case illustrates the need for transplant recipients and their healthcare providers to carefully consider the risk of severe infection associated with domestic animal exposure.

Peptide binding at the GLP-1 receptor.

The receptor for GLP-1 [glucagon-like peptide-1-(7-36)-amide] is a member of the 'Family B' of GPCRs (G-protein-coupled receptors) comprising an extracellular N-terminal domain containing six conserved cysteine residues (the N-domain) and a core domain (or J-domain) comprising the seven transmembrane helices and interconnecting loop regions. According to the two-domain model for peptide binding, the N-domain is primarily responsible for providing most of the peptide binding energy, whereas the core domain is responsible for binding the N-terminal region of the peptide agonists and transmitting the signal to the intracellular G-protein. Two interesting differences between the binding properties of two GLP-1 receptor agonists, GLP-1 and EX-4 (exendin-4), can be observed. First, while GLP-1 requires its full length to maintain high affinity, the eight N-terminal residues of EX-4 can be removed with little reduction in affinity. Secondly, EX-4 (but not GLP-1) can bind to the fully isolated N-domain of the receptor with an affinity matching that of the full-length receptor. In order to better understand these differences, we have studied the interaction between combinations of full-length or truncated ligands with full-length or truncated receptors.